Ambient Air Pollution and Population Health: Overview

Daniel Krewski and Daniel Rainham McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Ontario, Canada

European-funded thematic network on pollution and health. In November 2003 approximately 200 researchers, stake- NERAM is the Canadian Network for Environmental Risk holders, and policymakers from more than 40 countries gathered Assessment and Management, which fosters the integration of to discuss the science and policy implications of air pollution scientific knowledge and expertise to support efficient environ- and human health as part of the AIRNET/NERAM Strategies for Clean Air and Health initiative. The purpose of this paper mental protection practices and decision making. The purpose is to review the more than 35 research posters presented at the of this paper is to review the more than 35 research posters conference, including exposure, toxicological, and epidemiological presented at the AIRNET/NERAM conference. The studies studies of air pollution. Collectively, these papers support previous have been organized into the following areas: studies of air evidence that both short- and long-term exposures to particulate pollution exposure, studies of the effects of air pollution on air pollution have adverse population health impacts, including effects on children. Cellular studies also suggest that air pollution human and animal toxicology, epidemiological studies, and can cause mutagenic and oxidative effects, raising concerns about studies providing valuable insights using alternative method- carcinogenicity and cellular regeneration. Studies of biomarkers, ologies and approaches. We conclude with a summary of the such as Clara-cell proteins and lymphocyte damage assessment, research findings and speculate on some of the implications for provide further evidence of air pollution effects at the cellular the development of policy to prevent population health impacts level. Other studies have focused on improvements to measurement and sources of air pollution. These studies suggest that from air pollution exposures. particle mass rather than particle composition may be a more useful indicator of potential human health risk. It is well known that emissions from transportation sources are a major contrib- EXPOSURE ASSESSMENT utor to ambient air pollution in large urban centres. Epidemio- logic researchers are able to reduce bias due to misclassification Sources of Variation and improve exposure assessment models by allocating air pollu- As part of the HEAPSS project (Health Effects of Air tion exposure according to distance from traffic sources or land- use patterns. The close association between traffic patterns and Pollution on Susceptible Subpopulations), Aalto et al. (2003) air pollution concentrations provides a potential basis for the used an ultrafine particle database with information from five development of transport policies and regulations with population European cities, to quantify the risk of hospitalization and of health improvements as a primary objective. The results of the death due to air pollution. Particle measurement sites were research presented here present opportunities and challenges for selected to represent urban background concentrations. Initial the development of policies for improvements to air quality and reviews of the particle data suggest an increase in ultrafine human health. However, there remains the challenge of how best to achieve these reductions. particle concentrations is associated with decreasing latitude in the winter months and with temperature inversion events. The Aarnio et al. (2003) adjunct research on traffic-specific particle exposures improves estimates of the actual concen- In November 2003 approximately 200 researchers, stake- trations experienced while commuting in urban areas. Particle holders, and policymakers from more than 40 countries gath- samples were drawn from locations specific to commuting by ered to discuss the science and policy implications of air train, metro, bus, or by foot. Preliminary conclusions reveal pollution and human health as part of the AIRNET/NERAM significant differences between urban background and traffic- Strategies for Clean Air and Health initiative. AIRNET is a specific locations in terms of concentration exposures and particle size.

Accepted 10 February 2006. Particle Composition Address correspondence to Daniel Krewski, McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, One Exposure studies have also focused on the hypothesis that Stewart Street, Room 320, Ottawa, ON Canada K1N 6N5. E-mail: the physiological reaction to particulates will vary depending [email protected] or [email protected] on particle composition. Cassee et al. (2003) examined the

275 276 D. KREWSKI AND D. RAINHAM qualitative differences among particles collected from different long-term air pollution concentration series. Metz (2003) corre- sites throughout Europe. Aside from the usual increase in lated source emission contribution data with information on particle concentrations during the winter months, the study available air quality data to develop a model useful for fore- also found significant contrasts in chemical composition as a casting future particle emissions and ambient concentrations. function of location. For example, metal concentrations were These types of series will be useful for estimating the impact of higher in Rome, whereas higher concentrations of magne- population health interventions associated with technological sium and vanadium were found from samples collected in improvements, transportation policies, and strategies employed Amsterdam. In a similar study, De Berardis et al. (2003) studied to reduce human exposure, especially among susceptible the composition and physicochemical characteristics of parti- populations. cles less than 2.1 g/m3 in Rome using scanning electron microscopy (SEM) and ion chromatographic techniques. Initial conclusions indicate a predominance of particles originating HUMAN TOXICOLOGY from vehicular sources, except during winter, when particles are released through combustion of heating oil or methane gas Biomarkers for heating purposes. Exposure to specific chemicals associated Biomarkers are used to improve assessments of biolog- with carbonaceous particles will typically vary with climatic ical plausibility in the relationship between air pollutants and transportation patterns. and human health effects. Clara-cell proteins, a promising biomarker, have been identified as sensitive markers of increased permeability of the lung epithelial barrier, and an Source Apportionment increase in serum levels has been associated with ambient Urban populations experience heavier exposures to traffic- ozone concentrations. Ozone exposures under controlled labo- related air pollution concentrations. Frequency of exposures ratory conditions among healthy adults resulted in a signif- increases with the density of traffic and with traffic congestion, icant increase in serum levels of Clara-cell proteins up to a trend common in many large urban centers, and magni- 6 h after initial exposure (Blomberg et al., 2003). However, tude of exposure increases among higher density populations. the influence of serum baseline diurnal variations is uncertain However, it is interesting to note that a majority of expo- and further research is warranted. Research has also focused sure to traffic and combustion related by-products takes place on identification of specific biological reactions from expo- indoors. Ilacqua and Jantunen (2003) reported that volatile sure to fine particulates. Research has also shown that fine organic compounds (VOCs) from tailpipe emissions comprise particles may have direct or indirect effects on blood coagula- the largest contributor to personal exposure, with more than tion processes and thus physiological impacts affecting cardiac two-thirds of the exposure taking place indoors. Transportation function. To evaluate the biological effects of fine particles is also a source of particulate air pollution and is highly vari- Tarrona et al. (2003) examined a cohort of healthy adults able, depending on weather conditions and traffic flow densi- between the ages of 20 and 55 yr working in clean industrial ties. In the United Kingdom, for example, research has shown environments, such as the semiconductor and pharmaceutical that an average of 25% of particulate pollution originates from industries, and living in urban areas. Markers of blood coag- road transportation and that this figure rises to 75–80% on high ulation were assessed at three points—before the work shift, pollution days (O’Connell & Matthews, 2003). after the work shift, and after exposure to outdoor ambient air during commuting or social and domestic routines—with the Temporal Trends goal of providing a plausible biological explanation for the Epidemiological assessment of the population health risks ecologic link between exposure to particulate air pollution and from air pollution could not be performed without the construc- myocardial infarction. tion of high-quality, long-term data sets. Of particular interest are ultrafine particles, as research is beginning to reveal the inverse relationship between particle size and risk to health. Genotoxicity Particle concentrations are time and location dependent. For Genotoxic chemicals are able to cause damage to DNA but example, Marconi et al. (2003) found that ultrafine particle do not inevitably lead to the creation of cancerous cells (PTCL, concentrations were much greater in winter than in summer, 2004). Inorganic and organic compounds that dominate the were highly correlated with hours of high traffic volumes, and composition of fine particulate matter air pollution may cause were lower on weekends than on weekdays. They also found genotoxic health effects, although the extent of genotoxicity is that proximity to high traffic locations plays an important role not well known. Brits et al. (2003) collected fine particulate in determining exposure. Background sites characteristically matter from urban and industrial sites in Belgium to evaluate have particle concentrations up to 50% lower than with sites the mutagenic and cytotoxic properties. Particle mass concen- located near high traffic areas. Also of population health signif- trations of both PM10 and PM2.5 were significantly higher in the icance is the development of methods for the derivation of industrial area. Human alveolar epithelial cells were exposed OVERVIEW OF HEALTH EFFECTS 277 in vitro to particulate matter for a 48-h period to investigate an effect modifier in the relationship between exposure to toxicological potential. Although particles from both size frac- PAHs and genetic injury. Studies of the potential for oxida- tions showed no significant toxicity, the micronucleus frequen- tive damage to DNA were also performed to investigate the cies in binucleated cells were significantly increased, indicating differences between exposed and less exposed groups. Some potential mutagenetic effects. significant results were detected between cities, although most Gábelová et al. (2003) assessed the genotoxicity of the conclusions were mixed (Singh et al., 2003). Sram et al. (2003a, organic components associated with particulate air pollution. 2003b) used DNA adducts analysis and a common molecular The organic components of particulate matter were extracted cytogenetic technique called fluorescence in situ hybridization from particulates collected at three sites from three coun- (FISH) to assess genotoxic risk. tries. The organic components induced a seasonal and dose- The results are of interest for two reasons. First, the FISH dependent in vitro increase of DNA damage in human cells. technique seems to be an efficient tool to detect chromosomal Effects were most pronounced for coarse particles in the 2.5–10 aberrations and thus useful as a sensitive biomarker of exposure m diameter range. to PAHs. Second, the analysis detected significantly increased Guastadisegni et al. (2003) investigated the relationship FISH cytogenetic parameters in nonsmoking policemen and between the chemical composition of particulate matter air bus drivers (exposed group), indicating an association between pollution and toxicity. An analysis of 32 samples collected increased exposure to particulate air pollution with PAHs and from a variety of European metropolitan and rural areas sought potential genotoxic effects. to assess the oxidative activity of particles. The investigators created a synthetic model of the respiratory tract lining Source Toxicity fluid and measured the depletion rates of ascorbate, urate, and Exposure to air pollution, and fine particulate pollutants, reduced glutathione following a 4-h exposure to 50 g/ml can originate from either point or line (mobile) sources. As particle concentration. Inflammatory response was measured opposed to typical epidemiological investigations designed to by evaluating the release of arachidonic acid, tumor necrosis assess health risk within a population, toxicological studies factor alpha, and interleukin-6 from a macrophagic cell line. will assess the level and variability of chemicals within the The oxidative potential of particulate matter air pollution seems bloodstream or serum to determine the level of exposure to a strongly related to a capacity to induce arachidonic acid from specific pollutant source. From these studies it is then assumed the macrophages and can be explained by the bioavailability that these chemicals will lead to measurable health impacts of iron specific to every particle. However, these relationships or possible mortality. Individuals in a toxicological study are were only apparent in the coarse fraction. generally grouped according to level of exposure, for which The aim of the EXPAH studies (Effects of polycyclic distance can be used as a suitable proxy. aromatic hydrocarbons [PAHs] in environmental pollution on For example, Fierens et al. (2003) conducted a study to exogenous and endogenous DNA damage) is to evaluate the quantify the amount of dioxins, polychlorinated biphenyls role of PAHs as a source of genotoxic activities of organic (PCBs), and heavy metals in the bloodstreams of residents mixtures associated with particulate air pollution. The effect living in the vicinity of a municipal solid waste incinerator. A of DNA damage is monitored by determination of chromo- comparison or control group living in an unpolluted area was some aberration, and susceptibility in populations is studied used for statistical comparison, and information on lifestyle, by investigating the effect of metabolic polymorphisms in dietary, and occupational characteristics was also collected. carcinogen metabolism and DNA repair. A case-control design The study concluded that exposure to emissions from a munic- was adopted to evaluate genotoxocity in exposed and less- ipal solid waste incinerator can increase the body burden of exposed groups in the cities of Prague, Kosice, and Sofia. The dioxin and PCBs but that the increase is dependent on the exposed group consisted of police (as well as bus drivers in consumption of animal fat products from the local food chain. Sofia), and the control groups were volunteers who spent more The proposed interaction between exposure from the point than 90% of their time in indoor environments. The role of source and dietary intake provides an indication of the diffi- competing risks factors such as diet and other lifestyle factors culty involved when assessing toxic effects of pollution in a was also evaluated. localized ecosystem. As part of the EXPAH studies, Cebulska-Wasilewska Point sources of pollution may also have significant impacts et al. (2003) investigated cellular susceptibility to polycyclic on highly susceptible subpopulations as well as in the popula- aromatic hydrocarbons (PAHs). Damage to DNA was eval- tion. Lolova et al. (2003) investigated the relationship between uated as a function of lymphocyte repair competence. No air pollution emissions from a smelter plant and blood lead significant differences were detected between the referent and levels in children, as well as in placenta, maternal, and cord exposed groups, although residual damage to DNA and kinetic blood. Air quality and ambient lead and cadmium levels were repair is less efficient among those with greater exposure to determined from three fixed monitoring stations. Blood lead PAHs. Lymphocyte repair rates were also lower for those levels were analyzed from children residing close to the moni- with less education, implying a possible role of education as toring sites and from a control group not exposed to a specific 278 D. KREWSKI AND D. RAINHAM point source, as well as from 76 maternal/infant pairs. The the ongoing Adventist Smog and Health study (Abbey et al., investigators found that lead and cadmium concentrations in 1999), have consistently demonstrated associations between the vicinity of the smelter were above national guidelines, long-term exposure to particulate matter and mortality and have suggesting that the population is at risk of increased exposure played a pivotal role in the establishment of national air quality to these chemicals. The researchers also found that blood lead objectives in both the United States and Canada (Greenbaum levels in children living within the smelter area were signif- et al., 2001). Many newly developed European cohort studies icantly higher than among children living outside the area. have adopted advanced spatial techniques and will make an Furthermore, the results also indicate a significant relationship important contribution to improving the estimation of human between abnormal birth outcomes (preterm births) and signif- health risk from ambient air pollution. icantly higher than normal lead levels in maternal and cord The European Community Respiratory Health Survey blood. (ECRHS) consists of a 9-yr follow-up prospective survey Mobile sources of air pollution, such as particulate pollu- of more than 13,000 adults including data from 29 research tion from road traffic, also pose serious health risks. Since centres located in 14 countries. As part of the air pollution much of the air pollution in urban areas arises from motor working group, Götschi et al. (2003) are currently investigating vehicle emissions, recent research has begun to take interest correlations between surrogates of exposure to air pollution in the variation of health effects associated with distance from across 21 European centres and evaluating the influence of air road traffic sources, as well as the variation in particle toxicity pollution sampler location on air pollution exposure assess- associated with density of road traffic. Gerlofs-Nijland et al. ment. The SAPALDIA 2 (Swiss Cohort Study on Air Pollu- (2003) investigated how the toxic potency of particulate pollution and Lung Diseases in Adults) Swiss cohort study, part tion varied with levels of traffic exhaust emissions. Particles of the ECRHS study, is assessing associations of long-term were assessed for their toxic potential and grouped according air pollution exposure with the 10-yr course of respiratory to particle size and reactivity. Tests of toxicity were performed and atopic symptoms, diseases, and markers of respiratory in vitro (in rats) and in vivo (in humans) using indicators health and of atopy and cardiovascular health among 9651 of ascorbate depletion, arachidonic acid release, interleukin-6, adults. Participants have been followed for address changes and and damage to DNA (genotoxicity). The researchers found that mortality since 1991 and 83% of the original cohort is avail- toxicity varies with particle size, although both fine and course able for continued study. A geographic information systems particles have adverse health effects. They also found that (GIS)-based approach was used to derive individual expo- particles from locations with high-traffic areas induce more sure assignments from traffic-related air pollution exposures effects than those from lower traffic areas. while also taking into consideration historical ambient pollutant New research is also probing into the toxicological charac- levels and participant mobility patterns (Bayer-Oglesby et al., teristics of antioxidants as potential protection from vehicle- 2003). Although results are still forthcoming, the SAPALDIA related air pollution. de Burbure et al. (2003) investigated 2 study constitutes a novel approach to the creation of a cohort antioxidant status as a measure by selenium levels and lung from an original cross-sectional study and represents a novel response to NO2 in rats. Selenium-normal and selenium- approach for detecting the long-term health effects of low-level deficient rats were differentially exposed to NO2 concentra- air pollution. tions ranging from normal concentrations to acute exposures. Cohorts have also been created to assess the impacts of The conclusions suggest that antioxidants play an impor- air pollution on morbidity outcomes. A study called HEAPSS tant protective role in respiratory response to both acute and (Health Effects of Air Pollution on Susceptible Subpopula- long-term challenges from air pollutants such as NO . The 2 tions) was designed to assess whether air pollution increases the results also support previous research of Clara-cell proteins risk of first acute myocardial infarction (MI) or the subsequent (CC16) as excellent markers of increased lung permeability. risk of cardiac events among patients who have survived their Ironically, selenium may interact with CC16 antioxidants, first MI (Lanki et al., 2003). Using a common protocol, the resulting in decreased antioxidant production, thus depriving cohort will consist of approximately 27,000 cases of nonfatal the lung of its natural capacity to protect against foreign MI derived from hospital admission registries located in pollutants. Germany, Spain, Sweden, Italy, and Finland. Although pooled associations were generally weak, the researchers concluded EPIDEMIOLOGY that acute exposure to carbon monoxide (CO) and ultrafine particles (PM2.5) increases risk of hospitalization for new MI Cohort Studies even after controlling for the potential confounding effects of Cohort study designs afford an opportunity to investigate weather and personal health characteristics. the long-term health effects from exposure to air pollution. Many cohort studies of health impacts from air pollution are In North America, large cohort studies such as the Harvard limited by the quality and extent of exposure data available. Six Cities study (Dockery et al., 1993), the American Cancer For example, many older air pollution monitoring stations were Society studies (Pope et al., 1995; Krewski et al., 2003), and activated to monitor specific point-source pollutants resulting OVERVIEW OF HEALTH EFFECTS 279 from manufacturing or industrial processes and not for the ranged from 20 to 45 g/m3 for fine particles; however, values measurement of ambient exposures. In Scotland, however, from the traffic-related monitors revealed concentrations in the long-term (>50 yr) records exist for measurements of black upper end of the distribution at 37 and 43 g/m3 for Madrid smoke and sulfur dioxide (SO2). Yap et al. (2003) have linked and Rome, respectively. Cross-sectional analysis of health and this valuable exposure data set to health outcomes data derived air pollution data from 1999 reveal increased chronic and acute from three existing cohorts consisting of more than 26,000 effects on mortality in cities with higher vehicular particulate subjects; they are also able to link each subject to individual concentrations (Mücke et al., 2003). Vehicular traffic is also hospital admission data and/or to mortality records using the a major contributing source of ambient urban air pollution in Scottish Health Record Linkage System. Multilevel modeling Tblisi, Georgia. To investigate the potential for health impacts, and GIS techniques will allow for the investigation of potential Samadashvili (2003) examined the leading morbidity outcomes confounding and effect modification by individual and aggre- of children between the ages of 7 and 17 yr living either in an gate level factors, and long-term exposure data will enable area with high traffic related pollution concentrations or in a an examination of exposure latency durations and temporal suburban area with much lower concentrations. Children from variation in pollutant concentrations. Results of this work are the more polluted district were more likely to have some form forthcoming. of respiratory illness and were 2.5 times more likely to contract some form of skin disease.

Cross-sectional Studies Cross sectional studies measure the prevalence of health Time-series Studies outcomes or determinants of health in a population at a point Evidence of associations between air pollution and human in time or over a short period. This type of information can be health impacts is derived primarily from time-series studies. used to explore etiology, for example, the association between A time-series approach is used to associate daily fluctuations exposure to air pollution and any variety of health outcomes. in ambient air pollution levels with daily rates of mortality Heinrich et al. (2003) in the Bitterfeld study utilized data from or morbidity, and such studies have consistently demonstrated three cross-sectional surveys taken over a 7-yr period to deter- increased risk to health on or shortly following a day with mine temporal changes in the impact of ambient pollution on increased ambient pollution levels, in urban centers worldwide. children’s health. The study included a total of 5360 children The analysis of time-series data also requires careful consider- ranging in age from 5 to 7 yr. The children were administered ation of seasonal trends in the data, as well as adjustment for a questionnaire, and subsequent tests of spirometry, histamine important covariates such as climate and gaseous copollutants response, and blood analysis were employed to assess physi- (Burnett et al., 1995). ological response. Children from more polluted areas showed In Reggio Emilia, Italy, a time-series approach was adopted poorer respiratory health, and ambient particles were correlated to evaluate the short-term effects of urban air pollution with increased risk of allergenic sensitization. levels on children’s emergency visits from respiratory causes Another cross-sectional study has also reported acute effects (Bedeschi et al., 2003). Researchers used generalized additive of air pollution on respiratory conditions among susceptible regression models to develop risk estimates of emergency visits populations. The AUPHEP (Austrian Project on Health Effects after controlling for temporal and weather-related influences. of Particulates) project investigated the short-term effect of Statistically significant and positive associations were found particulate matter on lung function, morbidity, and mortality for NO2 (11% increase in emergency visits) and for PM10 (3% in three urban centers (Vienna, Linz, and Graz) and one less increase). An analogous statistical approach was adopted by polluted rural control area (Neuberger et al., 2003). The investi- Vigotti et al. (2003) to investigate the association between gators found fine particles to be associated with cardiovascular ambient air pollution (CO, NO2, and PM10) and presenta- mortality among the elderly of Vienna and with an increase in tions to the emergency room for respiratory-related complaints respiratory-related hospital admissions, and there was an asso- by children and elderly patients in Pisa, Italy. A significant ciation with lung function impairment among children in Linz. increase in emergency-room visits was confirmed for children Thus, despite overall improvements to air quality in Austria, and the elderly resulting from particulate pollution exposure, particulate matter and traffic-related air pollution still pose after controlling for weather and temporal variability. human health risks, especially for the elderly and children. An important but often overlooked consideration in the eval- More recently, epidemiological investigations have focused uation of time-series studies linking particulate air pollution on health effects from traffic-related air pollution—a large levels with health outcomes is the influence of specific metal source of urban ambient air pollution. The APHEIS (Air Pollu- concentrations located on the particle surface compared to the tion and Health: A European Information System) network has particle mass concentration alone. To examine this issue more collected air pollution concentration information for 26 Euro- thoroughly, Beverland et al. (2003) conducted a long-term pean cities, of which 2, in Madrid and Rome, have dedicated study to investigate the relationship between elevated respi- traffic-based monitors. Mean concentrations among all sites ratory and cardiovascular mortality and morbidity rates and 280 D. KREWSKI AND D. RAINHAM the variance of metal composition of PM10 in urban and rural OTHER STUDIES locations in Edinburgh, Scotland. The researchers used a novel Recent research contributions have illuminated the health air mass trajectory approach to determine the particle char- impacts of air pollution at subregulatory concentrations, and acteristics of air masses common to the Edinburgh area. Air have highlighted the need for researchers to consider the roles masses centered on the United Kingdom or originating from of human activity patterns and meteorology as influential in the east/central Europe were associated with a 25% greater concen- air pollution and health risk relationship. An extensive review tration of both PM10 and PM2.5 when compared to air masses of peer-reviewed published research on the health effects from other regions. A forward stepwise multiple-regression from ozone suggests positive significant associations to health modeling approach was adopted to examine the fraction of outcomes below the 40–80 ppb 8-h average range (Walton, water-soluble metal concentrations (Fe, Cu, Ni, V, Zn) as a 2003). Ambient concentrations of ozone below current Belgian constituent of particle mass. Generalized additive models were air quality standards have been associated with inflammatory used to investigate the associations between health outcomes changes in the airways of children (Nickmilder et al., 2003). and either particle mass or metal fractions after controlling for Research has also revealed the importance of considering time– particle mass. A positive, significant association was found activity data and exposures to common chemicals as potential between cardiovascular admission and a 10-g/m3 increase in risks to the development of respiratory and cardiopulmonary total PM10 concentrations; although similar associations were diseases such as asthma (Bernard et al., 2003). Moreover, atten- found for specific metal fractions, the risk estimates became tion should be directed toward a more thorough consideration statistically insignificant after adjustment for total particle mass of atmospheric risk factors than just air pollution. Air mass in the model. analysis and other meteorological approaches to controlling Another novel development in the use of time-series for the health impacts from variations in weather will help approaches to investigate air pollution-related health effects is to elucidate the potential for weather/air pollution interactions the integration of genotyping to identify susceptible subgroups and will enable public health authorities to develop population and to determine the role of gene variation as a determi- health impact prediction systems based on atmospheric risk nant of inflammatory response. In a proposed study, Peters factors (Michelozzi et al., 2003). et al. (2003), as part of the AIRGENE Study Group, will use time-series methods to determine the relationship between inflammatory response and air pollutants among survivors SUMMARY OF FINDINGS of myocardial infarction in six cities in Europe. Genotyping The health effects of air pollution research posters repre- techniques will be used to provide insight into the mecha- sent important new findings from more than 41 cities and nisms leading to inflammatory response in an effort to iden- metropolitan areas across Europe. Consistent with previous tify and define susceptible subpopulations and prevent the air pollution and health research, many studies found chil- exacerbation of cardiovascular disease from ambient particle dren to be particularly susceptible to ambient concentrations of concentrations. air pollution in urban areas, resulting in decreased respiratory Several issues associated with the adoption of time-series function and related morbidities. It is also clear that popula- approaches are noteworthy. First, although time-series analyses tion health impacts are evident from both short- and long-term provide important information about the effects of short-term exposures to PM (Glorennec & Monroux, 2003). At the cellular exposure on mortality, they are unable to identify effects with level, studies reveal air pollution to have potential mutage- a lag period longer than several weeks (Dominici et al., 2000, netic and oxidative effects, which raises serious concern for the 2003). Second, research has recently shown that time-series potential for oncogenicity and healthy cellular regeneration. approaches can lead to overestimation of risk as well as over- Studies of biomarkers, such as Clara-cell proteins and lympho- statement of the precision of risk estimates, due to conver- cyte damage assessment, present the possibility of identifying gence problems in the generalized additive model (Ramsay air pollution effects at the cellular level and contribute to the et al., 2003a, 2003b). A correction to this problem using more evidence of air pollution as a causal factor for human health stringent convergence criteria confirms that mortality is asso- impacts. ciated with short-term fluctuations in particulate air pollution At the other end of the spectrum, studies have focused on (HEI, 2003). Third, health effect estimates from time-series improvements to air pollution measurement and sources. For studies are sensitive to a number of assumptions, including example, a few studies have shown that it may be more prudent model and parameter selection, comparison of health effect and efficient to assess particle mass rather than particle compo- estimates to zero pollution levels, issues related to confounding sition as an indicator of potential human health risk. Studies from multipollutant mixtures, and nonstandardized reporting of the impact to health from air pollution are also moving methods (Sahsuvaroglu & Jerrett, 2003). It may be helpful upstream. It is well known that emissions from transportation in future research for investigators to explore more fully the sources are a major component of the total ambient air pollu- consequences of uncertainty in the calculation and reporting of tion concentration in large urban centers. From an epidemio- health risk estimates from exposure to air pollution. logical perspective, researchers are able to reduce bias due to OVERVIEW OF HEALTH EFFECTS 281 misclassification and improve exposure assessment models by ence/NERAM International Colloquium, “Strategies for Clean Air and allocating air pollution exposure according to distance from Health,” November. Bernard, A., Carbonelle, S., Nickmilder, M., Michel, O., Higuet, S., de traffic sources and/or land-use patterns. From a policy perspec- Burbure, C., Buchet, J.-P., Hermans, C., Dumont, X., and Doyle, I. tive, the close association between traffic patterns (frequency 2003. Lung hyperpermeability and asthma prevalence in schoolchil- and mode) and air pollution concentrations leads to the devel- dren: Unexpected associations with the attendance of indoor chlorinated swimming pools. Poster presented at the 2nd AIRNET Annual Confer- opment of transport policies and regulations with population ence/NERAM International Colloquium, “Strategies for Clean Air and health improvements as a primary objective. Health,” November. Beverland, I. J., Heal, M. R., Agius, R. M., Hibbs, L. R., and Elton, R. 2003. The metal content of airborne particles: Application to epidemiological research. Poster presented at the 2nd AIRNET Annual Confer- POLICY IMPLICATIONS ence/NERAM International Colloquium, “Strategies for Clean Air and The results of the research presented here provide many Health,” November. opportunities and challenges for the development of poli- Blomberg, A., Mudway, I., Forsberg, B., Nordberg, G., and Bernard, A. 2003. Clara cell protein (CC16) as a biomarker for ozone exposure in humans. cies for improvements to air quality and human health. Poli- Poster presented at the 2nd AIRNET Annual Conference/NERAM Inter- cymakers interested in morbidity and mortality related to national Colloquium, “Strategies for Clean Air and Health,” November. air pollution should be made aware that the moderate and Brits, E., Schoeters, G., and Verschaeve, L. 2003. Evaluation of the muta- prolonged exposures, rather than peak exposures, are respon- genicity of PM10 and PM2.5 collected in an industrial and urban area of Antwerp. Poster presented at the 2nd AIRNET Annual Confer- sible for a majority of human health effects. Of partic- ence/NERAM International Colloquium, “Strategies for Clean Air and ular concern are the critical pollutants—respirable forms of Health,” November. particulate matter, carbon monoxide, nitrogen oxides, and Burnett, R. T., Dales, R., Krewski, D., Vincent, R., Dann, T., and Brook, J. R. 1995. Associations between ambient particulate sulfate and admissions to volatile organic compounds—that have been linked expressly Ontario hospitals for cardiac and respiratory diseases. Am. J. Epidemiol. to vehicle and transportation-related emissions. The results 142:15–22. from epidemiological research suggest there is insufficient Cassee, F. R., Bloemen, H. J., Boere, A. J., Fokkens, P. H., Leseman, D. L., evidence to depart from assumptions of linearity in associ- Catani, G., Johansen, B. V., Halatek, T., and Dybing, E. 2003. Qualitative differences in particulate air pollution at different locations throughout ations between air pollution and human health. Benefits to Europe (RAIAP). Poster presented at the 2nd AIRNET Annual Confer- health may be realized from any reductions in air pollution, ence/NERAM International Colloquium, “Strategies for Clean Air and inter alia pollution sources from transportation. Policymakers Health,” November. Cebulska-Wasilewska, A. 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